In primates, axons from the left and right eyes terminate in monocular laminae of the lateral geniculate body. From this nucleus, geniculostriate projections to primary visual cortex (V1) continue to reflect either left or right eye input and terminate in layer IVC of V1 where they are arranged in a system of roughly parallel alternating stripes known as ocular dominance columns (ODCs). In non-human primates, the organization of these columns has been studied by histological stains and auto radiography (Hubel and Wiesel 1977, LeVay et al. 1985, Kennedy et al. 1976), by micro electrode recordings (Hubel and Wiesel 1976), real-time optical imaging using voltage sensitive dyes (Salzberg et al. 1973), and by optical imaging of intrinsic signals (Tso et al. 1990, Grinvald et al. 1986, Grinvald et al. 1991). In humans, the ODCs have been demonstrated post-mortem in striate cortex by histochemical staining for cytochrome oxidase (Horton et al. 1984, Horton et al. 1990), but a noninvasive technique for examining human striate cortex organization on the scale of cortical functional subunits has not been available. The hemodynamic-response mechanism that allows visualization of orientation columns and ODCs in awake monkeys by optical imaging of intrinsic signals demonstrates that corticovascular responses to visual stimuli can be localized to the columnar level in several mammalian species (Tso et al. 1990, Grinvald et al. 1986, Grinvald et al. 1991). The Blood Oxygen Level Dependent (BOLD) technique upon which the vast majority of cortical mapping using functional Magnetic Resonance Imaging (fMRI) is based, is also sensitive to the hemodynamic changes in the local vasculature, which suggests that, in principle, cortical columns could be mapped noninvasively using fMRI as well. While the optical data demonstrate that the capillary bed hemodynamic response is sufficiently confined to a cortical column, localization of the mapping signal in fMRI with respect to the active cortical area and vascular tree is still quite controversial. At issue here is the belief that BOLD signals coming from large vessels may dominate those coming from the microvasculature, particularly on conventional MRI scanners. This is problematic, because it raises concern that macrovascular changes distal to the actual site of neuronal activity can occur. This would place a fundamental limit on correlation of fMRI activation maps and neuronal activity. For fMRI studies using clinically available hardware, ~ 3 mm in-plane resolution and ~ 5 mm slices are typical because of the limited signal-to-noise ratio (SNR) available in high temporal resolution imaging sequences (Callaghan 1993). Using the same high-resolution fMRI pulse-sequence with imaging hardware and parameters optimized at three different field strengths, we have found that the SNR at 4 T is at least 4 times higher than at the much more commonly available 1.5 T field strength (Gati et al. 1995). This increase is sufficiently large to attempt imaging of ODCs in human V1, which are approximately 0.8 to 1 mm on a side for a column and 5-10 mm long in humans (Horton et al. 1984, Horton et al. 1990). Using a simple visual paradigm in combination with an optimized radio-frequency (RF) coil, head restraints, sub-voxel image registration and the enhanced SNR provided by 4 T, we have been able to demonstrate adjacent image pixels in human V1 that respond primarily to left or right eye photic input. We identify them as ocular dominance columns. Grinvald, A., Lieke, E., Frostig, R. D., Gilbert, C. D. and Wiesel, T. N. Functional architecture of cortex revealed by optical imaging of intrinsic signals. 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